Systemic gene therapy with anti-angiogenic factors inhibits spontaneous breast tumor growth and metastasis in MMTVneu transgenic mice

Tumor growth and metastasis are angiogenesis-dependent. The possibility of inhibiting tumor growth by interfering with the formation of new vessels ha s recently raised considerable interest. We previously reported that it is possible to inhibit primary tumor growth and metastasis in a transgenic mod el of spontaneous breast tumor, which shows many similarities to its human counterpart (including ability to metastasize) by intratumoral administrati on of a DNA construct carrying the murine angiostatin cDNA driven by liposo mes. Here we report that it is also possible to achieve this goal by a syst emic (intraperitoneal) delivery of therapeutic DNA constructs carrying gene s coding for mouse and human anti-angiogenic factors which include angiosta tin, endostatin and TIMP-2. These findings may be relevant to the design of therapeutic interventions in humans.